The identification of factors affecting the susceptibility to infectious diseases is essential toward reducing their burden on the human population. The ABO blood type correlates with susceptibility to malaria and other infectious diseases. Due to the structural similarity between blood antigen B and Gal&alpha;1-3Gal&beta;1-(3)4GlcNAc-R (&alpha;-Gal), we hypothesized that self-tolerance to antigen B affects the immune response to &alpha;-Gal, which in turn affects the susceptibility to infectious diseases caused by pathogens carrying &alpha;-Gal on their surface. Here we found that the incidence of malaria and tuberculosis, caused by pathogens with &alpha;-Gal on their surface, positively correlates with the frequency of blood type B in endemic regions. However, the incidence of dengue fever, caused by a pathogen without &alpha;-Gal, was not related to the frequency of blood type B in these populations. Furthermore, the incidence of malaria and tuberculosis was negatively correlated with the anti-&alpha;-Gal antibody protective response. These results have implications for disease control and prevention.

fig2: Correlation between ABO blood types and disease. (a) Correlation analysis between the frequencies of blood types A and B (Supplementary Table 1) and malaria incidence in Africa in 2000 and 2015 (Supplementary Table 2). Spearman's rank correlation coefficient tests were significant for blood types A (Spearman r⩽−0.50, P⩽0.004) and B (Spearman r⩾0.55, P⩽0.002) in both years 2000 and 2015. (b) Correlation between the number of deaths due to malaria in 2014 and the frequencies of blood types A (Spearman r=−0.19, P=0.21) and B (Spearman r=0.50, P=0.01) in Africa. (c) Correlation between the percentage of reduction in malaria incidence (2015 vs 2000) and the frequencies of blood types A (Spearman r=0.28, P=0.09) and B (Spearman r=−0.46, P=0.01) in Africa. (d) Correlation between the frequencies of blood types A (Spearman r=−0.54, P<0.0001) and B (Spearman r=0.51, P<0.0001) and the incidence of tuberculosis in Africa, Asia, America and Europe. (e) Correlation between the frequencies of blood types A and B and the incidence of dengue fever in Africa, Asia, America and Europe.

Mentions:
To address this hypothesis, we collected data on the incidence of malaria, a disease affecting 200 million people yearly and caused by Plasmodium spp. parasites,29 and the frequency of blood types A, B, O and AB in countries from Africa, Asia, Europe and America to perform correlation analyses (Supplementary Table 1). Blood-type B is present in <20% of the population in all countries from America and Europe, while this blood type is highly prevalent in malaria endemic countries from Africa and Asia (Figure 1a and Supplementary Figure 1). The frequency of blood-type B was negatively correlated with the frequency of blood-type A in Africa, Asia and Europe, but not in America (Supplementary Figure 2). Using the malaria incidence spanning from 2000 to 2015 (Supplementary Table 2), we observed that African countries with the highest incidence of malaria have the minimum and maximum frequencies of blood types A and B, respectively (Figures 1b and 2a). The number of deaths due to malaria in Africa in 2014 (Supplementary Table 3) was also positively correlated with the frequency of blood-type B, but not the frequency of blood type A (Figure 2b). Malaria incidence decreased in Africa from 2000 to 2015,21 a result that correlated with a reduction in the frequency of blood type B (Figure 2c). However, no correlation was found between the frequencies of blood types O or AB and malaria incidence (Supplementary Figure 3).

fig2: Correlation between ABO blood types and disease. (a) Correlation analysis between the frequencies of blood types A and B (Supplementary Table 1) and malaria incidence in Africa in 2000 and 2015 (Supplementary Table 2). Spearman's rank correlation coefficient tests were significant for blood types A (Spearman r⩽−0.50, P⩽0.004) and B (Spearman r⩾0.55, P⩽0.002) in both years 2000 and 2015. (b) Correlation between the number of deaths due to malaria in 2014 and the frequencies of blood types A (Spearman r=−0.19, P=0.21) and B (Spearman r=0.50, P=0.01) in Africa. (c) Correlation between the percentage of reduction in malaria incidence (2015 vs 2000) and the frequencies of blood types A (Spearman r=0.28, P=0.09) and B (Spearman r=−0.46, P=0.01) in Africa. (d) Correlation between the frequencies of blood types A (Spearman r=−0.54, P<0.0001) and B (Spearman r=0.51, P<0.0001) and the incidence of tuberculosis in Africa, Asia, America and Europe. (e) Correlation between the frequencies of blood types A and B and the incidence of dengue fever in Africa, Asia, America and Europe.

Mentions:
To address this hypothesis, we collected data on the incidence of malaria, a disease affecting 200 million people yearly and caused by Plasmodium spp. parasites,29 and the frequency of blood types A, B, O and AB in countries from Africa, Asia, Europe and America to perform correlation analyses (Supplementary Table 1). Blood-type B is present in <20% of the population in all countries from America and Europe, while this blood type is highly prevalent in malaria endemic countries from Africa and Asia (Figure 1a and Supplementary Figure 1). The frequency of blood-type B was negatively correlated with the frequency of blood-type A in Africa, Asia and Europe, but not in America (Supplementary Figure 2). Using the malaria incidence spanning from 2000 to 2015 (Supplementary Table 2), we observed that African countries with the highest incidence of malaria have the minimum and maximum frequencies of blood types A and B, respectively (Figures 1b and 2a). The number of deaths due to malaria in Africa in 2014 (Supplementary Table 3) was also positively correlated with the frequency of blood-type B, but not the frequency of blood type A (Figure 2b). Malaria incidence decreased in Africa from 2000 to 2015,21 a result that correlated with a reduction in the frequency of blood type B (Figure 2c). However, no correlation was found between the frequencies of blood types O or AB and malaria incidence (Supplementary Figure 3).

The identification of factors affecting the susceptibility to infectious diseases is essential toward reducing their burden on the human population. The ABO blood type correlates with susceptibility to malaria and other infectious diseases. Due to the structural similarity between blood antigen B and Gal&alpha;1-3Gal&beta;1-(3)4GlcNAc-R (&alpha;-Gal), we hypothesized that self-tolerance to antigen B affects the immune response to &alpha;-Gal, which in turn affects the susceptibility to infectious diseases caused by pathogens carrying &alpha;-Gal on their surface. Here we found that the incidence of malaria and tuberculosis, caused by pathogens with &alpha;-Gal on their surface, positively correlates with the frequency of blood type B in endemic regions. However, the incidence of dengue fever, caused by a pathogen without &alpha;-Gal, was not related to the frequency of blood type B in these populations. Furthermore, the incidence of malaria and tuberculosis was negatively correlated with the anti-&alpha;-Gal antibody protective response. These results have implications for disease control and prevention.